Inhaled Fentanyl Aerosol in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
Inhaled Fentanyl Aerosol in Healthy Volunteers: Pharmacokinetics and Pharmacodynamics
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DOI：
10.1213/ane.0b013e3182691898
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发表时间：
2012-11-01
影响因子：
5.7
通讯作者：
Gan, Tong J.
中科院分区：
文献类型：
--
作者：
MacLeod, David B.;Habib, Ashraf S.;Gan, Tong J.
背景技术背景：将强效阿片样物质快速递送至体循环是有效治疗急性和慢性发作性疼痛的重要特征。通过肺部途径递送不同的阿片类药物一直不一致，通常导致药物的生物利用度低。Staccato（R）芬太尼吸入是一种手持式吸入器，在单次吸气过程中产生单次定量的雾化芬太尼。该气雾剂具有高纯度（>= 98%），颗粒大小（1至3.5微米）最适合肺部吸收。在交叉阶段，10名受试者分别接受静脉注射芬太尼25 μ g和吸入芬太尼25 μ g。剂量递增阶段是吸入芬太尼（50至300 μ g）的多剂量、随机、双盲、安慰剂对照、单阶段剂量递增研究。连续的血液采样进行了8小时内，给药后，以确定的药代动力学曲线，并进行了一系列瞳孔作为衡量药效学effects.RESULTS：在交叉阶段的吸入和IV芬太尼的药代动力学曲线显示出类似的峰值动脉浓度和曲线下面积。吸入芬太尼达到最大浓度的时间略短于静脉注射芬太尼，分别为20.5秒和31.5秒。在剂量递增阶段的重复剂量的管理导致可预测的，剂量依赖性的血清concentration.CONCLUSIONS：这项研究表明，单剂量的吸入芬太尼的药代动力学曲线是可比的IV管理。（Anesth Analg 2012;115：1071-7）
BACKGROUND: Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato (R) Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (>= 98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption.METHODS: We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 mu g and inhaled fentanyl 25 mu g on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 mu g). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect.RESULTS: In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations.CONCLUSIONS: This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration. (Anesth Analg 2012;115:1071-7)